Ultracytochemical demonstration of Ca(++)-ATPase activity in the rat cardiac muscle.

Ca(++)-activated adenosine triphosphatase (Ca(++)-ATPase) was investigated in the rat cardiac muscle at neutral pH using tricine buffer. Reaction products indicating Ca(++)-ATPase activity were localized on the myocardial sarcolemma, sarcoplasmic reticulum, myofilaments, luminal and abluminal surfaces of capillary endothelium plasmatic membrane. The verification of the main enzymatic characteristics of Ca(++)-ATPase localization activity using this cytochemical procedure is under discussion.     

Blood oxygen transport and pro-oxidant-antioxidant state during liver reperfusion

Indices of blood oxygen transport (hemoglobin-oxygen affinity, pCO2, pH, pO2, etc.) and prooxidant-antioxidant state (Schiff bases, conjugated dienes, catalase, retinal, alpha-tocopherol) were measured in rabbit blood and the liver during postischemic reperfusion. Hepatic ischemia was induced for 30 min by ligation of a hepatica propria, and reperfusion lasted for 120 min. Hepatic ischemia worsened blood oxygen transport. Restoration of arterial blood flow did not result in improvement of oxygen delivery. Moreover, marked metabolic acidosis was observed throughout 2 hr of reperfusion. Ischemia induced a shift of oxyhemoglobin dissociation curve to the right. This shift persisted after restoration of hepatic arterial blood flow facilitating increased oxygen transport to tissues. Changes in blood oxygen transport during hepatic ischemia/reperfusion were accompanied with high activity of free radical processes. During reperfusion, the largest increase in content of lipid peroxidation products and the greatest fall of some antioxidant levels except catalase were observed indicating impairment of liver prooxidant-antioxidant balance. The results showed that activation of lipid peroxidation and a decrease in some antioxidant levels during hepatic reperfusion were associated with lowering of hemoglobin-oxygen affinity and suggest participation of the latter in impairment of prooxidant-antioxidant balance.     

Artificial Tears Inhibit the Development of Experimental Immune-mediated Blepharoconjunctivitis

Purpose To investigate whether treatment with artificial tears inhibits the development of experimental immune-mediated blepharoconjunctivitis (EC).Methods Brown Norway rats were immunized with ovalbumin (OVA) or ragweed (RW) emulsified in complete Freunds adjuvant. Fourteen days after immunization, the rats were challenged with the same antigen (Ag) in eye drops. Treated rats were administered artificial tears by eye drops immediately after, 15min after, or 30min after the Ag challenge. Treatment doses of 2, 4, or 8 drops per eye were evaluated. Twenty-four hours after the Ag challenge, the rats were killed and their eyes were harvested for histological studies.Results Treatment with artificial tears immediately after and 15min after challenge with partially insoluble RW Ag suppressed infiltration of inflammatory cells into the conjunctiva. Inhibition was not observed at any time following challenge with OVA Ag, which is a soluble protein. The treatment dose of artificial tears administered did not affect the extent of inhibition of EC following challenge with either Ag.Conclusions Treatment with artificial tears by eye drops inhibited the development of EC induced by the partially insoluble RW Ag when administered within 15min of the Ag challenge. Jpn J Ophthalmol 2004;48:530–534 © Japanese Ophthalmological Society 2004     

Paradoxical enhancement of spinal-cord-evoked potentials rostral and caudal to the site of progressive cord compression in the cat

STUDY DESIGN: Analysis of the sequential waveform changes of the spinal-cord-evoked potentials (SCEPs) associated with progressive cord compression in the cat. OBJECTIVES: To document the phenomenon of paradoxical enhancement of SCEPs despite conduction abnormalities and to evaluate its possible significance. SETTING: Kochi Medical School, Kochi, Japan. METHODS: SCEPs were recorded simultaneously at four serial intervertebral levels, from T6-7 to T9-10 caudal to, and at three serial levels from T2-3 to T4-5 rostral to the compression site at T5-6 following epidural stimulation at L6 in 14 cats. RESULTS: Caudal to the compression site, the area of negative peak significantly increased toward maximal values of 277+/-36 (mean+/-SE), 151+/-9 and 110+/-4% as compared to the baseline precompression values (100%) at T6-7, T7-8, and T8-9, respectively. Rostral to the compression site, the area of negative peak significantly increased before subsequent deterioration and reached 105+/-2, 106+/-2, and 104+/-2% at T4-5, T3-4, and T2-3, respectively. The onset of negative peak enhancement, recorded either caudal or rostral to the compression site, showed a close temporal correlation (r>0.8, P&<0.001) with that of the prolongation in latency of SCEPs at T2-3. CONCLUSIONS: A progressive focal conduction block induced by compression of the spinal cord can paradoxically enhance the ascending SCEPs both caudally and, though less consistently, rostrally, representing a warning of the impending risk of paraplegia.     

Affinity of hemoglobin for oxygen and prooxidant-antioxidant equilibrium after administration of lipopolysaccharide during correction of the L-arginine—NO pathway

Effects of correction of the L-arginine—NO pathway on the fever reaction, oxygen transport function of the blood, and prooxidant-antioxidant equilibrium in rats injected intramuscularly with lipopolysaccharide were studied. pH, Pco₂, Po₂, and the index of hemoglobin oxygen affinity (p50) were measured in mixed venous blood. Levels of Schiff bases, α-tocopherol, and catalase activity were determined in erythrocytes and in the liver, kidneys, and heart. NO synthase inhibitor attenuated the fever reaction and decreased p50 to 28.89±0.83 mm Hg (in rats administered with lipopolysaccharide, p50 was 34.21±1.63 mm Hg). The increase in the content of Schiff bases and the exhaustion of the antioxidant system in erythrocytes and tissues were less pronounced in rats injected with the NO synthase inhibitor than in animals receiving lipopolysaccharide only. Various parameters of the prooxidant-antioxidant equilibrium correlated with p50. Thus, hemoglobin oxygen affinity and NO are important factors involved in the maintenance of the prooxidant-antioxidant equilibrium in the body. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 616–619, June, 1999     

Prooxidant-antioxidant state of the organism during oxidative stress and correction of the L-arginine-NO system

The prooxidant-antioxidant balance in rats with oxidative stress was studied during correction of the L-arginine-NO system. Oxidative stress was induced by intravenous injection of E. coli lipopolysaccharide. Under conditions of oxidative stress the prooxidant-antioxidant imbalance was least pronounced during selective correction of the L-arginine-NO system. L-Arginine and nonselective NO synthase inhibitor had little protective effect. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 4, pp. 368–370, April, 2006     

Simulation of roller compaction using a laboratory scale compaction simulator

A method for simulation of the roller compaction process using a laboratory scale compaction simulator was developed. The simulation was evaluated using microcrystalline cellulose as model material and ribbon solid fraction and tensile strength as key ribbon properties. When compacted to the same solid fractions, real and simulated ribbons exhibited similar compression behavior and equivalent mechanical properties (tensile strengths). Thus, simulated and real ribbons are expected to result in equivalent granulations. Although the simulation cannot account for some roller compaction aspects (non-homogeneous ribbon density and material bypass) it enables prediction of the effects that critical parameters such as roll speed, pressure and radius have on the properties of ribbons using a fraction of material required by conventional roller compaction equipment. Furthermore, constant ribbon solid fraction and/or tensile strength may be utilized as scale up and transfer factors for the roller compaction process. The improved material efficiency and product transfer methods could enable formulation of tablet dosage forms earlier in drug product development.